Objective: The inhibition of oxidative stress is among the most relevant pleiotropic effects of statins. The mechanism by which statins exert their antioxidant effect in vivo is still undefined. NADPH oxidase is among the most important sources of reactive oxygen species involved in atherosclerotic disease. Methods/Results- We developed an ELISA to evaluate serum levels of soluble-gp91(phox), the catalytic core of phagocyte NADPH oxidase. In a cross-sectional study performed in 30 hypercholesterolemic patients and in 20 controls, serum soluble-gp91(phox) and urinary isoprostane, a marker of oxidative stress, were measured. The 2 variables were also measured in hypercholesterolemic patients, randomized to diet (n=15), or diet plus atorvastatin (10 mg daily, n=15) and followed for 30 days. Compared to controls, hypercholesterolemic patients had higher and significantly correlated (R=0.71; P<0.001) serum soluble-gp91(phox) (P<0.001) and urinary isoprostanes (P<0.001). After follow-up, the statin-allocated group showed a significant reduction of soluble-gp91(phox) (-33%, P<0.01), that paralleled that of isoprostanes (-37%, P<0.01) and cholesterol (-25%, P<0.01). The diet-allocated group showed only a weak reduction of cholesterol.
Conclusions: Our study demonstrates that statins exert an antioxidant effect via inhibition of soluble gp91(phox) expression.